7PYV

Crystal structure of human UBA6 in complex with the ubiquitin-like modifier FAT10

Summary for 7PYV

• Entry DOI: 10.2210/pdb7pyv/pdb
• Descriptor: Ubiquitin-like modifier-activating enzyme 6,Ubiquitin-like modifier-activating enzyme 1,Ubiquitin-like modifier-activating enzyme 6, UBD (2 entities in total)
• Functional Keywords: ubiquitin activating enzyme uba6, human leukocyte antigen (hla)-f adjacent transcript 10(fat10), fat10ylation, post-translational modification, ubiquitin-like modifier, hydrolase
• Biological source: Homo sapiens (Human); More
• Total number of polymer chains: 3
• Total formula weight: 251379.96

Authors

Li, S.,Truongvan, N.,Schindelin, H. (deposition date: 2021-10-11, release date: 2022-08-24, Last modification date: 2024-01-31)

Primary citation

Truongvan, N.,Li, S.,Misra, M.,Kuhn, M.,Schindelin, H.
Structures of UBA6 explain its dual specificity for ubiquitin and FAT10.
Nat Commun, 13:4789-4789, 2022

PubMed Abstract: The covalent modification of target proteins with ubiquitin or ubiquitin-like modifiers is initiated by E1 activating enzymes, which typically transfer a single modifier onto cognate conjugating enzymes. UBA6 is an unusual E1 since it activates two highly distinct modifiers, ubiquitin and FAT10. Here, we report crystal structures of UBA6 in complex with either ATP or FAT10. In the UBA6-FAT10 complex, the C-terminal domain of FAT10 binds to where ubiquitin resides in the UBA1-ubiquitin complex, however, a switch element ensures the alternate recruitment of either modifier. Simultaneously, the N-terminal domain of FAT10 interacts with the 3-helix bundle of UBA6. Site-directed mutagenesis identifies residues permitting the selective activation of either ubiquitin or FAT10. These results pave the way for studies investigating the activation of either modifier by UBA6 in physiological and pathophysiological settings.

PubMed: 35970836
DOI: 10.1038/s41467-022-32040-6

Experimental method

X-RAY DIFFRACTION (3.27 Å)